N-(substituted-benzoyl) aminoaceto- and aminopropionitriles



nite States atent "Ce 3,457,294

Patented July 22, 1969 and hydrochloride, hydrobromide and sulfate saltsthere- 3,457,294 of, hydrogen, loweralkyl-branched or cyclic, aryl,

ggwgm k i fgg AND hydroxyloweralkyl, loweralkoxyloweralkyl, and cyano-Aldo J Crovetii l l l Ft fres f and Maynette V Neundorf loweralkyl; R ishydrogen or methyl; and R" is hydrogen, loweralkyl-branched or cyclic,or aryl. The terms L 1 Bl if, Ill. t Abb ttL b ator' s North i s j sfgigg f g or m 5 loweralkyl or loweralkoxy include the straight and N D iFil d A 22, 1966, s N 544,375 branched alkyl and alkoxy radicalscontaining from one I t, Cl, (107 121/52 to four carbon atoms.Cycloalkyl includes radicals of U.S. Cl. 260-465 7 Claims from three tosiX carbon atoms.

The members of this new series of compounds have 10 antibacterial aswell as antifungal and antiprotozal ac- ABSTRACT OF THE DI C O E tivity.The in vitro activity of some of these compounds, Compounds having theformula; agalnst the indicated microorganisms, is illustrated in X thefollowing tables. The first table identifies the noted Y W 0 R compoundswith the indicated radicals referring to the g L general formula whilethe second table illustrates the minimum inhibitory concentration of thenoted com- Z R R pounds against representative organism-s.

Staph. Proteus Chaetonium E.' T. W X Y Z R R R n aureus vulgarisglobosum tenella vaginalis Cpd.:

1 H 2.01 4N0, H H H H 0 6.2 0. 012% 50 2 H .01 4.1m, H cm H H 0 6.2 0.012% 100 3 H 2-01 4-NO3 H 33 H H 0 0.05%

CH3-CH2 4 H 2-o1 3-N0g 5-NO2 H H H 0 10 100 10 5 2-01 a-Noz 4-01 5-NO; HH H 0 10 100 100 1 Concentration in parts per million. 2 Percentconcentration 1n chicken feed.

in which n is 0 to 4, W is chloro, nitro, or methyl; X is Additionally,the compounds of the present invention hydrogen, chloro, nitro, amino,or methoxy; Y is hydr0- possess herbicidal activity, both terrestrialand aquatic, gen, chloro, nitro, or methyl; and Z is hydrogen or nitro;and for this reason can be employed to control plant and wherein Rrepresents diloweralkylamino loweralkyl growth. The representativeherbicidal activity of some of and physiologically-acceptable saltsthereof, hydrogen, 35 these compounds is illustrated in the followingtables. loweralkyl-branched or cyclic, aryl, hydroxyloweralkyl, Theindicated radicals refer to the general formula above.

EFFECTIVE PRE-EMERGENCE ACTIVITYAGAINST CORN AND ALFALFA AT A LEVEL OF100 p.p.m.

ELODEA AT A LEVEL OF 10 p.p.m.

1 3-NOz 4-C1 fi-NO; H Methyl H H 0 2 2-01 3-NOz 5-NO H H H H 0loweralkoxyloweralkyl, and cyanoloweralkyl; R is hydro- The compounds ofthe present invention are prepared gen or methyl; and R" is hydrogen,loweralkyl-branched by the reaction of an appropriate aminonitrile andan of cyclic, y Which Compounds have antibacterial as appropriatebenzoyl halide in a suitable reaction medium Well as antiflmgal andantipfotolal activitysuch as water or an inert solvent, i.e., benzene,ether,

chloroform, dimethylformamide, dimethylacetamide, or dimethoxyethane inthe presence of an acid acceptor, for example, sodium hydroxide, sodiumcarbonate, pyridine, or trialkylamine.

The following examples are presented to illustrate Y X w o R theinvention.

gamma,

I l Example I.N-(2-chloro-4-nitrobenzoyl) Z R R" aminoac tonitrile 1nWhlCh n 15 0 to 4, W is chloro, nitro, or methyl; X is e hydrogen,chloro, nitro, amino, or methoxy; Y is hydrogen, chloro, nitro, ormethyl; and Z is hydrogen or nitro; A Solutlon 0f Sodium Y d a andwherein R represents diloweralkylaminoloweralkyl 41.4 g. (0.39 M) sodiumcarbonate in 200 ml. water is This invention relates to novel nitrilederivatives and to a process for producing same. More particularly, theinvention relates to nitrile compounds having the formula:

stirred and chilled to 10 C. To this is carefully added 60 g. (0.39 M)aminoacetonitrile hydrogen sulfate. Holding the temperature at 10 C., 84g. (0.39 M) of 2-chloro-4-nitrobenzoyl chloride is added dropwise.Stirring in the cold is continued an hour followed by stirring at roomtemperature for 2 to 48 hours. The tan solid is filtered off, washedwith a little water and crystallized from 50% ethanol, using activatedcharcoal to decolorize. After filtration and drying, 69 g. (74%) ofN-(2-chloro-4-nitrobenzoyl)aminoacetonitrile is recovered, M.P. 126-127.

Example 2.N-(4-amino-3,S-dichlorobenzoyl) -f1- aminopropionitrile Asolution of 3.5 g. (0.05 M) fl-aminopropionitrile and g. (0.05 M)triethylamine in 30 ml. of dimethylacetamide is stirred and heated to 40C. To this is added a Warm solution of 11.2 g. (0.05 M)4-amino-3,5-dichlorobenzoyl chloride in 20 ml. dimethylacetamide. Afterstirring at room temperature for another 2 hours, the mixture is dilutedwith Water to 2 liters to obtain a white precipitate. This is filteredoff and dried. After crystallization from benzene, 9.5 g. (74%)N-(4-amino-3,5-dichlorobenzoyl)-fi-aminopropionitrile is recovered, M.P.208209.

Example 3.N-B-(2-chloro-4-nitrobenzoyl) -N-ethylaminopropionitrile Asolution of 9.8 g. (0.1 M) N-ethylaminopropionitrile and 10.1 g. (0.1 M)triethylamine in 40 ml. dimethylformamide is stirred rapidly as asolution of 22 g. (0.1 M) 2-chloro-4-nitrobenzoyl chloride in 30 ml.dimethylformamide is added. The mixture is stirred and heated (steambath) for an hour and then allowed to remain at room temperature for 20hours. Most of the solvent is removed by vacuum distillation and theoily residue distilled. The fraction, B.P. 208-2l2/0.6 mm., weighs 8.3g. (30%), n 1.5640, and isN-fl-(2-chloro-4-nitrobenzoyl)-N-ethylaminopropionitrile.

Example 4.N- (2-ch1oro-4-nitrooenzoyl) -N-isopropylaminoacetonitrile Asolution of 9.8 g. (0.1 M) N-isopropylaminoacetonitrile and 10.1 g. (0.1M) triethylamine in 50 ml. dry benzene is stirred as 22 g. (0.1 M)2-chloro-4-nitrobenzoyl chloride in 50 ml. dry benzene is addeddropwise. When addition is complete, the mixture is stirred and refluxedfor 2 hours and then cooled to room temperature. The triethylaminehydrochloride is filtered oil? and the filtrate concentrated to an oil.This is crystallized from 95% ethanol using activated charcoal todecolorize. After vacuum drying, 17.1 g. (61%)N-(2-chloro-4-nitrobenzoyl)- N-isopropylaminoacetonitrile is recovered,M.P. 120 122.

In like manner, reacting the appropriate aminonitrile and benzoylchloride in the manner exemplified will result in the formation of thefollowing compounds of the present invention. In the following table,the column entitled Method refers to the foregoing examples as themethod employed in making each of the compounds exemplified in Examples5 to 70.

Found Calculated M.P., 0. Formula R" 11 Method Ora-MOO CUEU U I mama 2147-148 CmHmChNaO 10 3-Cl 4-NHz 5-0] 147-149 0 E ClgNaO 2 158-160CmHnClzNaO 10 3-01 -NHz 5-01 126-127 C 173-175 C 109-110 C 116-118 C101-103 C cot-(OOH P th-11 11 51 11 1 CzH5 1-9 2-Cl 4-N0z

